Numerous studies from this laboratory have investigated the interaction of insulin with circulating mononuclear cells. The present project involves studies in vivo insulin-dependent diabetes mellitus (IDDM) and glucocorticoid excess. We have attempted to characterize the insulin receptor of the human erythrocyte. Mononuclear cells and erythrocytes both have insulin receptors whose functions are altered by conditions of health and disease. Comparative studies of these two different cell types show that in some cases their insulin receptor status may be similar, but that the actual regulation of their receptor concentration may differ. The effects of sulfonylurea drugs on erythrocytes and mononuclear cells were also studied. These drugs do not seem to produce their clinical effect by direct interaction with the insulin receptor.